Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Random gene activation helps ulcer bug escape immune system

22.11.2004


The bacterium that causes ulcers and contributes to stomach cancers uses a clever interaction between two genes to randomly tighten and loosen its grip on the stomach, according to a study by researchers at Washington University School of Medicine in St. Louis and Umeå University in Sweden.



Helicobacter pylori often binds tightly to cells of the stomach lining to feed, but the newly identified interaction ensures that a small reservoir of bacteria are always more loosely connected. This reservoir is much more likely to survive if the host mounts a strong immune response. "Basically, if you’re holding onto someone’s T-shirt and they start punching you hard, you’d like to be able to let go," jokes Douglas Berg, Ph.D., Alumni Professor of Molecular Microbiology and an author of the study. "Any savvy bacteria are going to want to be able to do the same."

New insights into how H. pylori sticks to and then releases from the stomach wall will advance efforts to design better drugs and vaccines against the bacterium, which is estimated to be present in more than half of the world’s population. Most H. pylori infections in the U.S. and other industrialized nations can be treated with antibiotics, but treatments are too costly for many sufferers in underdeveloped nations, where the bacteria’s pervasiveness and poor sanitation significantly increase the risk of repeat infections. In addition, resistance to standard drug therapies is a major problem in these countries.


The study appears in the online edition of Proceedings of the National Academy of Sciences. It will appear in print in the journal on November 30. Researchers at Umeå University led by Anna Arnqvist, Ph.D., associate professor of molecular biology and medical biochemistry and a former Washington University predoctoral student, studied a Swedish strain of H. pylori. They focused on BabA, a protein that binds to Lewis B antigen receptor, a carbohydrate structure on the surface of stomach cells. Because they help organisms stick to particular targets in a glue-like fashion, BabA and proteins like it are collectively known as adhesins.

One of the Swedish strain’s two copies of the gene for BabA is "silent," or blocked from use by damage in a region of DNA normally involved in the gene’s activation. The second copy is missing an essential portion of DNA, making it completely nonfunctional. "This suggested that the strain doesn’t make BabA protein at all, making it equivalent in that regard to about one-third of all the other clinical isolates of H. pylori scientists have studied," Berg says.

Given that the strain didn’t appear to produce BabA protein, the bacteria should have been unable to get a grip on the Lewis B receptor. However, scientists found that a small minority of the bacteria still stuck very tightly to Lewis B.

Researchers then determined that this resulted from the bacteria recombining DNA from the silent BabA gene and DNA from the gene for a similar protein, BabB. Scientists aren’t sure what, if anything, BabB sticks to, but they do know that its similarities to BabA include biochemical "hooks" at the beginning and end of the protein. These hooks anchor the proteins in the bacteria’s cell wall. The BabA gene’s middle section encodes the glue that makes the protein stick. The rare bacteria that could grip Lewis B had spliced that middle section from the silent BabA gene into BabB, providing themselves with the equivalent of a working BabA gene and its protein product.

BabA-BabB gene recombination is relatively rare because characteristics of the segments of DNA being combined make them technically difficult for the bacteria to splice together. In addition, the BabB gene has a built-in genetic feature that allows the gene to turn on and off irregularly as the bacteria reproduce. "The BabB gene has a highly repetitive section that has a tendency to slip when the bacteria copies its DNA prior to cell division," Berg explains. "These slips can introduce extra repeats or delete them, shifting how the gene is translated from DNA to protein in a way that’s likely to halt protein synthesis by introducing a premature stop signal."

The net result, according to Berg, is that the bacteria’s ability to stick to the Lewis B receptor is metastable--in every generation, a small number of the new bacteria will switch from a tight grip to no grip, or vice-versa. "This metastability is likely an important component of the bacteria’s ability to adapt to host immune system responses," Berg says.

Berg and his Swedish colleagues are currently working to better understand BabB, investigating, among other things, whether the gene has a role to play on its own as a producer of a bacterial adhesin or only acts as a random enabler of BabA. Among the approximately 30 H. pylori surface proteins so far known to scientists, researchers have found other pairs of closely related genes. Included in these pairs are other genes that code for surface adhesins. "We also will take a close look at some of these pairs," Berg says. "We’re eager to find out whether they contain variations of this special regulatory system in BabA and BabB, or whether they control the strength and specificity of H. pylori adherence in other ways."

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>